Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives

被引：4
|
作者：
Zhang, Honglin [1 ]
Chen, Yiyan [1 ]
Liu, Qiuyu [1 ]
Xiao, Wen-Wen
Shao, Li-Dong [1 ]
Pan, Zheng-Hong [2 ]
Chen, Chuan-Huizi [1 ]
Li, Dashan [1 ]
机构：
[1] Yunnan Univ Chinese Med, Sch Chinese Mat Med, Yunnan Key Lab Southern Med Resources, Kunming 650500, Peoples R China
[2] Guangxi Zhuang Autonomous Reg & Chinese Acad Sci, Guangxi Inst Bot, Guangxi Key Lab Funct Phytochem Res & Utilizat, Guilin 541006, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2023年 / 83卷
基金：
中国国家自然科学基金;
关键词：
Toosendanin; Triple negative breast cancer; Structure-activity relationships; Mechanism;
D O I：
10.1016/j.bmcl.2023.129187
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.
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页数：6
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